Pimozide and pyrogen-induced fever in rabbits.
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Biomedical subjects
Publications and source records attributed to P Lechat.
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Micromolar concentrations of 4-aminopyridine (4-AP) were able to increase the amplitude of the end-plate current in frog neuromuscular junction blocked either by d-tubocurarine or by low Ca++ high Mg++ medium. The end-plate potential was also increased. These effects were reversible. The changes in the end-plate current amplitude observed after 4-AP treatment had no effect on the end-plate current time course. There was no significant difference in the resting membrane potential or mean amplitude and frequency of spontaneous miniature end-plate potentials in the presence of 4-AP. The quantal content of the end-plate potential was increased in every preparation tested and the minimal synpatic delay was lengthened in a dose-related way. 4-AP did not modify the dependence of the amplitude of the end-plate current on membrane potential. In the presence of 4-AP, the time constant of the falling phase of the end-plate current remained an exponential function of the membrane potential. The end-plate current equilibrium potential was unaffected by 4-AP. The increase in the amount of acetylcholine released by nerve impulse induced by 4-AP occurs without modification in the calcium cooperativity. The authors suggest that 4-AP, by prolonging the presynaptic action potential, could increase calcium concentration in the nerve terminal and, thus, the transmitter release.
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Cultures of beating rat myocardial cells brought into contact with various human sera during 24 hours were infused with isoprenaline. The isoprenaline-induced positive chronotropic effect (IIPCE) was not found with all sera. IIPCE was present in all the male sera, but was absent in the cases of clinically beta-blocked pindolol treated men. IIPCE was present only in about 50% of the female sera, menopaused or not. IIPCE was absent in 95% of the sera of pregnant women in the late phase of pregnancy. This suggests the presence in female sera, especially during pregnancy, of a circulating factor capable of "in vitro" inhibition of isoprenaline-induced positive chronotropic effect.
During acute asphyxia in pentobarbital-narcotized cats, the elevation in plasma potassium level was parallel to that of PCO2. From the time when PO2 reached its minimum, the elevation in serum potassium was higher than that of plasma potassium. The increase of the difference between serum and plasma potassium values seems therefore to be more related to hypoxia than hypercapnia; it could be due to membrane alteration of blood cells.
Peritoneal macrophages in culture are blocked in the G0 phase of the cell cycle, but retain many of their functional characteristics such as phagocytic ability. Peritoneal macrophages have been thought to be a terminal cell type. It has been investigated whether such properties could be modified by a substance released in acute inflammatory exudates. For this purpose a pleural exudate obtained from rats injected with dextran (40,000) 4 hours before, was centrifuged to eliminate cells, sterilized by filtration on Millipore filter 0.22 mum and diluted 50% with 199 medium culture. This medium was used to treat normal and activated peritoneal macrophages in culture. The effects were observed 24, 48, 72, 96 hours after the beginning of treatment. An enhancement of spreading and capacity of phagocytosis was observed 24 hours after the beginning of treatment. After 48 hours, the number of cells incorporating tritiated thymidine increased and became highest 4 days later. These phenomena were also obtained with pleural exudate of inbred rats (Lewis, Wag) treating macrophages of the same strain and with rat pleural exudate treating mouse macrophages. No effects were observed with dextran alone. The chemical nature of the stimulatory factor remains to be elucidated.
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The influence of pretreatment with the antihistaminic, mepyramine, or with the histamine liberator 48/80 was studied on the volume and the histamine content of pleural exudates induced in rats by intrapleural injection of turpentine, silver nitrate or carrageenan. The fluorometric determination of histamine was performed in the exudates collected at different times after injection of the irritant. In control animals the histamine levels were different from those previously found by the authors using biological assays. In rats pretreated with mepyramine or compound 48/80, the effects observed varied according to the nature of the irritant used to induce pleurisy.
When given orally in elevated but nonlethal doses (150 to 450 mg/kg, on 2 consecutive days), glafenine induces in rats (body weight 100 g) a transient nephritis with an increase in blood urea, hypertrophy of adrenals, and some changes in the serum proteinogram. These effects do not appear to be due to the 4-amino-7-chloroquinoline structure from which glafenine is derived, as they are not observed with the structural analogue chloroquine given at equimolar doses under the same conditions. Further, they do not appear to be due to glycerol, the by-product of metabolic glafenine hydrolysis. The responsible molecule appears to be either glafenine itself or its acid metabolite 4-(0-carboxyphenylamino) 7-chloroquinoline.
4-aminopyridine (4-AP) at micromolar concentrations, increases the end-plate potential amplitude in curarized preparations and the mean quantal content in every preparation tested, but the spontaneous release is not modified by 4-AP. These results can explain the anticurare activity observed in the wole animal or in vitro. 4-AP prolongs the falling phase of the muscle action potential without change in the muscle membrane potential.
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The action of prostaglandins E1 and A2 was studied on the proliferation and the phagocytosis of mouse peritoneal macrophages in culture. The proliferation was not stimulated by prostaglandins E1 and A2, but the phagocytosis was increased by prostaglandin A2 and decreased by prostaglandin E1. These actions could be correlated with the regulatory role of prostaglandins.
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The effects of 4-aminopyridine (4-AP) on guinea pig myocardial ventricular isolated strips were studied by means of intracellular microelectrodes. 4-AP increased the maximal depolarization velocity and decreased the effects of quinidine. In contrast to adrenaline, 4-AP antagonized the effects of MnCl1, but was ineffective against the alterations induced by a sodium poor solution. These findings support the suggestion that 4-AP modifies the electrophysiological membrane properties probably by increasing the Na+ inward current.
The uptake of non esterified fatty acids (NEFA), from a medium supplemented with 10% of calf serum, by rat myocardial cells cultured during 8 days, without renewal of the medium, was identical whatever the values of partial pressures of oxygen in the medium. Cellular cholesterol level was reduced when air or oxygen (+5% CO2) was blown into culture bottles; it was enhanced by gassing with nitrogen 24 h later. Cellular NEFA level was reduced by air, but not by oxygen blowing; it was enhanced by gassing with nitrogen 24 h later. The variations observed may originate from pertubations of NEFA beta-oxidation.